American Cyanamid Company

Shin S Tseng

Joseph William Epstein

John P Dusza

Herbert J Brabander

Jeremy Ian Levin

Andrew S Tomcufcik

Walter E Meyer

Jannie S Baker

Novel compounds of the formula ##STR1## wherein n is an integer from 1 to 4 inclusive; R.sub.1 represents a mono-or disubstituent of hydrogen, lower alkyl(C.sub.1 -C.sub.3), lower alkoxy(C.sub.1 -C.sub.3), halogen, nitro or trifluoromethyl; R.sub.2 is cyano, carboxamido, ethyl carboxylate or halogen; R.sub.3 is hydrogen, straight or branched chain lower alkyl(C.sub.1 -C.sub.3), alkenyl(C.sub.2 -C.sub.3), alkynyl(C.sub.2 -C.sub.3), cycloalkyl(C.sub.3 -C.sub.6), hydroxyalkyl(C.sub.1 -C.sub.3), dimethylaminoalkyl(C.sub.1 -C.sub.3), ethylcarboxylate, alkyl(C.sub.1 -C.sub.13)carbonyl, 1-(methylethyl)acetamide, cyclohexylethyl, phenyl, mono-or disubstituted phenyl (wherein the phenyl substituent is halogen, trifluoromethyl, lower alkyl(C.sub.1 -C.sub.3) or lower alkoxy(C.sub.1 -C.sub.3)), benzyl, mono-or disubstituted benzyl (wherein the benzyl substituent is halogen, lower alkyl(C.sub.1 -C.sub.3), lower alkoxy(C.sub.1 -C.sub.3) or trifluoromethyl), benzoyl, 4-methoxybenzoyl, straight or branched chain alkyl(C.sub.2 -C.sub.3)phenyl, 4-chlorophenylphenylmethyl, 1,3-benzodioxol-5-ylmethyl, 1,3-benzodioxol-5-yl, 2-furanylcarbonyl, 2-pyrimidinyl, 2-pyridinyl, 4-morpholinyl-2-oxoethyl, 1-pyrrolidinyl-2-oxoethyl, bis(4-fluorophenyl)methyl, phenylcarboxamido, mono- and disubstituted phenylcarboximido (wherein the phenyl substituents is halogen, trifluoromethyl or lower alkyl(C.sub.1 -C.sub.3)), adamantanoyl, 3-phenoxypropyl,5-chloro-2-methoxyphenylacetamide, (2-oxo-1-pyrrolidinyl)-2-butynyl, phenylmethylcarboxylate, or (2-phenyl-2H-1,2,3-triazol-4-yl)methyl; R.sub.4 and R.sub.5 are independently hydrogen or lower alkyl(C.sub.1 -C.sub.3); the dotted line between positions 6 and 7 of the pyrimidine ring represents the presence or absence of a double bond; and the pharmacologically acceptable salts thereof: methods of producing them; therapeutic compositions containing them: and methods of using them to treat anxiety, hypertension, depression, senile dementia, cognitive defects and other neural behavior problems in warm-blooded animals.

Method of treating cognitive and related neural behavioral problems

Novel N-((dialkylamino)methylene)-substituted-pyrazolo(1,5-a)pyrimidine-3-carbox amide and N-((dialkylamino)methylene)-substituted-4,5-dihydropyrazolo-(1,5-a)-pyrimi dine-3-carboxamide compounds are disclosed which are useful as neurotropic and/or anxiolytic and/or anti-hypertensive agents in mammals.

N-(dialkylamino)methylene)-substituted

Novel compounds of the formula ##STR1## wherein n is an integer from 1 to 4 inclusive; R.sub.1 represents a mono- or disubstituent of hydrogen, lower alkyl(C.sub.1 -C.sub.3), lower alkoxy (C.sub.1 -C.sub.3), halogen, nitro or trifluoromethyl; R.sub.2 is cyano, carboxamido, ethyl carboxylate or halogen; R.sub.3 is hydrogen, straight or branched chain lower alkyl (C.sub.1 -C.sub.3), alkenyl (C.sub.2 -C.sub.3), alkynyl(C.sub.2 -C.sub.3), cycloalkyl(C.sub.3 -C.sub.6), hydroxyalkyl(C.sub.1 -C.sub.3), dimethylaminoalkyl(C.sub.1 -C.sub.3), ethylcarboxylate, alkyl(C.sub.1 -C.sub.13)carbonyl, 1-(methylethyl)acetamide, cyclohexylethyl, phenyl, mono- or disubstituted phenyl (wherein the phenyl substituent is halogen, trifluoromethyl, lower alkyl(C.sub.1 -C.sub.3) or lower alkoxy (C.sub.1 -C.sub.3)), benzyl, mono- or disubstituted benzyl (wherein the benzyl substituent is halogen, lower alkyl(C.sub.1 -C.sub.3), lower alkoxy(C.sub.1 -C.sub.3) or trifluoromethyl), benzoyl, 4-methoxybenzoyl, straight or branched chain alkyl(C.sub.2 -C.sub.3)phenyl, 4-chlorophenylphenylmethyl, 1,3-benzodioxol-5-ylmethyl, 1,3-benzodioxol-5-yl, 2-furanylcarbonyl, 2-pyrimidinyl, 2-pyridinyl, 4-morpholinyl-2-oxoethyl, 1-pyrrolidinyl-2-oxoethyl, bis(4-fluorophenyl)methyl, phenylcarboxamido, mono- and disubstituted phenylcarboximido (wherein the phenyl substituents is halogen, trifluoromethyl or lower alkyl (C.sub.1 -C.sub.3)), adamantanoyl, 3-phenoxypropyl, 5-chloro-2-methoxyphenylacetamide, (2-oxo-1-pyrrolidinyl)-2-butynyl, phenylmethylcarboxylate, or (2-phenyl-2H-1,2,3-triazol-4-yl)methyl; R.sub.4 and R.sub.5 are independently hydrogen or lower alkyl(C.sub.1 -C.sub.3); the dotted line between positions 6 and 7 of the pyrimidine ring represents the presence or absence of a double bond; and the pharmacologically acceptable salts thereof; methods of producing them; therapeutic compositions containing them; and methods of using them to treat anxiety, hypertension, depression, senile dementia, cognitive defects and other neural behavior problems in warm-blooded animals.

4-[(substituted)alkylcarbonyl]-4,5-dihydro and

Novel N-((dialkylamino)methylene)-substituted- pyrazolo(1,5-a)pyrimidine-3-carboxamide and N-((dialkylamino) )methylene-substituted-4,5-dihydropyrazolo-(1,5-a)-pyrimidine-3-carboxamid e compounds are disclosed which are useful as neurotropic and/or anxiolytic and/or anti-hypertensive agents in mammals.

N-((dialkylamino)methylene)-substituted pyrazolo

Novel 2,4,8-trisubstituted-3H,6H-1,4,5a,8a-tetraazaacenaphthylene-3,5 (4H)-diones and 2,4,8-trisubstituted-4,5-dihydro-5-thioxo-3H, 6H-1,4,5a,8a-tetra-azaacenaphthylen-3-ones are disclosed which are useful antihypertensive and anxiolytic agents.

2,4,8-Trisubstituted-3H,6H-1,4,5A,8A-tetraazaacenaph

This disclosure describes 1-substituted-1,2-dihydro-4-[substituted)phenyl]imidazo[1,5-a]pyrimidine-8 -carbonitriles which are useful as antihypertensive agents and/or as antidepressant agents in mammals.

1-substitute-1,2-dihydro-4-((substituted)phenyl)imidazo-[1,5-a]

Novel compounds of the formula ##STR1## wherein n is an integer from 1 to 4 inclusive; R.sub.1 represents a mono- or disubstituent or hydrogen, lower alkyl(C.sub.1 -C.sub.3), lower alkoxy(C.sub.1 -C.sub.3), halogen, nitro or trifluoromethyl; R.sub.2 is cyano, carboxamido, ethyl carboxylate or halogen; R.sub.3 is hydrogen, straight or branched chain lower alkyl(C.sub.1 -C.sub.3), alkenyl(C.sub.2 -c.sub.3), alkynyl(C.sub.2 -c.sub.3), cycloalkyl(C.sub.3 -C.sub.6), hydroxyalkyl(C.sub.1 -C.sub.3), dimethylaminoalkyl(C.sub.1 -C.sub.3), ethoxycarbonyl, alkyl(C.sub.1 -C.sub.13)carbonyl, 1-(methylethyl)acetamide, cyclohexylethyl, phenyl, mono-or disubstituted phenyl (wherein the phenyl substituent is halogen, trifluoromethyl, lower alkyl(C.sub.1 -C.sub.3) or lower alkoxy(C.sub.1 -C.sub.3)), benzyl, mono- or disubstituted benzyl (wherein the benzyl substituent is halogen, lower alkyl(C.sub.1 -C.sub.3), lower alkoxy(C.sub.1 -C.sub.3) or trifluoromethyl), benzoyl, 4-methoxybenzoyl, straight or branched chain alkyl(C.sub.2 -c.sub.3)phenyl, (4-chlorophenyl)phenylmethyl, 1,3-benzodioxol-5-ylmethyl, 1,3-benzodioxol-5-yl, 2-furanylcarbonyl, 2-pyrimidinyl, 2-pyridinyl, 4-morpholinyl-2-oxoethyl, 1-pyrrolidinyl-2-oxoethyl, bis(4-fluorophenyl(methyl, phenylcarboxamido, mono- and disubstituted phenylcarboximido (wherein the phenyl substituents is halogen, trifluoromethyl or lower alkyl(c.sub.1 -C.sub.3)), adamantanoyl, 3-phenoxypropyl, 4[2-[(5-chloro-2-methoxyphenyl)amino-2-oxo-ethyl], (2-oxo-1-pyrrolidinyl-2-butynyl, phenylmethylcarboxylate, or (2-phenyl-2H-1,2,3-triazol-4-yl(methyl; R.sub.4 and R.sub.5 are independently hydrogen or lower alkyl(C.sub.1 -C.sub.3); the dotted line between positions 6 and 7 of the pyrimidine ring represents the presence or absence of a double bond; and the pharmacologically acceptable salts thereof: methods of producing them; therapeutic compositions containing them: and methods of using them to treat anxiety, hypertension, depression, senile dementia, cognitive defects and other neutral behavior problems in warm-blooded animals.

4-[(substituted) alkylcarbonyl]-4,5-dihydro- and

This disclosure described novel 5-(substituted-amino)-8-(substituted-phenyl)-3H,6H, -1,-4,5a,8a-tetraazaacenaphthylen-3-ones useful for the treatment of cognitive and related neural behavioral disorders in mammals.

5-(Substituted-amino)-8-(phenyl or

Substituted-6H,8H-pyrimido[1,2,3-cd]purine-8,10(9H)-diones and substituted-6H,10H-pyrimido[1,2-cd]purin-10-ones which are useful as cognition enhancing agents, anxiolytic agents and/or antihypertensive agents in the treatment of cognitive and relative neutral behavioral problems, anxiety and hypertension in mammals.

Substituted-6H,8H-pyrimido-[1,2,3-cd]purine-8,10-(9H)-diones and

This disclosure describes novel 4,8-disubstituted-1,2-dihydro- and -1,2,3,4-tetrahydro -imidazo-[1,5-a] pyrimidines useful as antihypertensive agents and/or as anxiolytic agents in mammals and as intermediates for the synthesis of biologically active compounds.

4,8-disubstituted-1,2-dihydro and 1,2,3,4-tetrahydroimidazo-[1,5-a]

Novel compounds having the following structural formula: ##STR1## wherein - - - may represent the presence of a double bond between the C.sub.6 and C.sub.7 position, Ia, or the absence of a double bond between the C.sub.6 and C.sub.7 position, Ib; R.sub.1 is selected from the group consisting essentially of hydrogen, bromo, chloro, carbamoyl, carboxyl, carboxyalkoxyl where alkoxyl is (C.sub.1 -C.sub.3), cyano, --CO--CF.sub.3, COONa, ##STR2## --CO--C(CH.sub.3).sub.3, and ##STR3## where X is hydrogen, cyano, halogen and nitro; R.sub.2, R.sub.4 and R.sub.5 may be hydrogen and lower alkyl (C.sub.1 -C.sub.3); R.sub.3 is hydrogen, alkyl (C.sub.1 -C.sub.3), ##STR4## where R.sub.7 and R.sub.8 may be the same or different and are selected from the group consisting essentially of hydrogen, halogen, alkyl (C.sub.1 -C.sub.3), nitro, alkoxy (C.sub.1 -C.sub.3), trifluoro-methyl, acetylamino or N-alkylacetylamino where alkyl is (C.sub.1 -C.sub.3), and R.sub.3 may also be selected from a monovalent radical selected from the class consisting essentially of 3-thienyl, 2-pyridinyl, 3-pyridinyl and 4-pyridinyl, either of said pyridinyl radicals being optionally substituted with an alkyl radical R.sub.9, where alkyl is (C.sub.1 -C.sub.4), and the structures of the monovalent 2-pyridinyl, 3-pyridinyl and 4-pyridinyl moieties are depicted respectively as: ##STR5## R.sub.6 is hydrogen or alkyl-(C.sub.1 -C.sub.3); pharmaceutical compositions of matter containing the above-defined compounds; methods for using the compounds as anxiolytic agents, antihypertensive agents or antidepressant agents in mammals; processes for the preparation of the compounds.

4,5-dihydro and 4,5,6,7-tetrahydropyrazolo(1,5-A)-pyrimidines

This disclosure describes certain pyrazolo[1,5-a]pyrimidines useful as hypotensive and/or anxiolytic agents, or as agents for the treatment of cognitive and related neural behavioral problems in mammals.

Pyrazolo[1,5-a]pyrimidines

This disclosure describes novel pyrazolylpiperazines useful as hypotensive agents in mammals and as intermediates for the preparation of certain pyrazolo[1,5-a]pryrimidines.

Growing community of inventors

Bridgewater, NJ, United States of America

Shin S Tseng